Organelle Ca2+/CAM1-SELTP confers somatic cell embryogenic competence acquisition and transformation in plant regeneration.

Somatic cell totipotency in plant regeneration represents the forefront of the compelling scientific puzzles and one of the most challenging problems in biology. How somatic embryogenic competence is achieved in regeneration remains elusive. Here, we discover uncharacterized organelle-based embryogenic differentiation processes of intracellular acquisition and intercellular transformation, and demonstrate the underlying regulatory system of somatic embryogenesis-associated lipid transfer protein (SELTP) and its interactor calmodulin1 (CAM1) in cotton as the pioneer crop for biotechnology application. The synergistic CAM1 and SELTP exhibit consistent dynamical amyloplast-plasmodesmata (PD) localization patterns but show opposite functional effects. CAM1 inhibits the effect of SELTP to regulate embryogenic differentiation for plant regeneration. It is noteworthy that callus grafting assay reflects intercellular trafficking of CAM1 through PD for embryogenic transformation. This work originally provides insight into the mechanisms responsible for embryogenic competence acquisition and transformation mediated by the Ca2+/CAM1-SELTP regulatory pathway, suggesting a principle for plant regeneration and cell/genetic engineering.

The significance and prognostic value of multifocal papillary thyroid carcinoma in children and adolescents.

INTRODUCTION: The prognostic value of multifocality in paediatric papillary thyroid carcinoma (PTC) patients remains a subject of debate. This study aimed to explore the clinical significance and prognostic value of multifocality in children and adolescents with PTC. METHODS: This study retrospectively analysed the clinicopathological characteristics and postoperative follow-up data of 338 PTC patients aged ≤ 20 years from May 2012 to July 2022. The clinical and pathological characteristics of 205 patients with unifocal lesions and 133 patients with multifocal lesions were compared. A logistic regression model evaluated the relationship between multifocal lesions and disease recurrence/persistence in children and adolescents with PTC. Based on the median follow-up time of children with multifocal PTC, 114 patients with multifocal PTC older than 20 years were added, and the clinicopathological characteristics were compared between the 133. paediatric/adolescent patients and 114 adult patients with multifocal PTC. RESULTS: Among the paediatric and adolescent patients, over a median follow-up time of 49 months, 133 had multifocal disease and 205 had unifocal disease. Multifocal PTC patients exhibited stronger invasiveness in the form of extrathyroidal extension, tumour diameter, lymph node metastasis, and distant metastasis. Multifocality (OR 2.68; p = 0.017), lateral lymph node metastasis (OR 2.85; p = 0.036), and distant metastasis (OR 4.28; p = 0.010) were identified as independent predictive factors for the recurrence/persistence of disease. Comparing the paediatric/adolescent vs. adult multifocal patients, the former demonstrated greater tumour invasiveness. Lateral lymph node metastasis (OR 6.36; P = 0.012) and distant metastasis (OR 3.70; P = 0.027) were independent predictive factors for recurrence/persistence of disease in multifocal patients, while age was not (OR 0.95; P = 0.455). CONCLUSION: Tumour multifocality independently predicts persistent/recurrent disease in paediatric and adolescent PTC patients.

Age estimation from median palatine suture using computed tomography reconstructed 3D images: a comparison of Northern and Southwestern Chinese populations.

To investigate the potential of computed tomography (CT) images of median palatine suture (MP) for adult age estimation in the Northern and Southwestern Chinese populations. A total of 1110 cranial CT scans from individuals aged 10-79 years, including 557 northern Chinese and 553 southwestern Chinese, were collected for analysis. After volume reformation and multiplanar reconstruction, a total of 20 slices of median palatine suture were selected from each individual. The closure of sutures was analyzed into four stages, and the cumulative scores of 20 slices were recorded as the suture closure score (SCS). The correlations between SCS and age were compared among the two Chinese populations residing in diverse geographic regions. Regression models were established for age estimation. The estimation accuracy was evaluated based on the test set. The mean absolute error (MAE) and the correlation between predicted age and chronological age were calculated to evaluate estimation accuracy. The SCS of MP exhibited a significant correlation with age (0.613, northern male; 0.678, southwestern male; 0.730, northern female; 0.704, Southwestern female; 0.662, total). Furthermore, there were statistically significant differences in SCS among different regions and sex groups (p < 0.001). The cubic regression model had the highest R2 value in all subjects, especially among Northern females and Southwestern males, while the power and quadratic regression models showed the highest R2 value in Northern males and Southwestern females, respectively. In the test set, the Northern cohort demonstrated a lower MAE (9.06 ± 7.32 years, males; 9.17 ± 5.28 years, females) compared to the Southwestern cohort (9.19 ± 7.49 years, male; 10.61 ± 6.83 years, female). Additionally, it was observed that males exhibited a lower MAE than females in both regional groups. This study demonstrated the potential utility of CT images of the MP for age estimation in Chinese populations, emphasizing the significance of incorporating regional and sex factors within this context.

Separase is recruited to mitotic chromosomes to dissolve sister chromatid cohesion in a DNA-dependent manner.

Sister chromatid separation is triggered by the separase-catalyzed cleavage of cohesin. This process is temporally controlled by cell-cycle-dependent factors, but its biochemical mechanism and spatial regulation remain poorly understood. We report that cohesin cleavage by human separase requires DNA in a sequence-nonspecific manner. Separase binds to DNA in vitro, but its proteolytic activity, measured by its autocleavage, is not stimulated by DNA. Instead, biochemical characterizations suggest that DNA mediates cohesin cleavage by bridging the interaction between separase and cohesin. In human cells, a fraction of separase localizes to the mitotic chromosome. The importance of the chromosomal DNA in cohesin cleavage is further demonstrated by the observation that the cleavage of the chromosome-associated cohesins is sensitive to nuclease treatment. Our observations explain why chromosome-associated cohesins are specifically cleaved by separase and the soluble cohesins are left intact in anaphase.

Effects of spinal mobilization on physical function in patients with stroke: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to identify, critically appraise, and synthesize current evidence regarding the effects of spinal mobilization on physical function in patients with stroke. Three databases, PubMed, Embase, and Scopus, were searched from inception to March 15, 2024. Randomized controlled trials comparing the effects of spinal mobilization to conventional therapy were eligible for inclusion. Methodological quality was assessed using the Physiotherapy Evidence Database scale. Meta-analyses were performed to determine the effects of spinal mobilization. Nine randomized controlled trials were included, with a total of 294 patients with stroke. All included studies were evaluated as good or above for quality assessment. No adverse events related to spinal mobilization were reported. Compared to conventional therapy, spinal mobilization demonstrated significantly improved forward head posture (SMD: 1.00, 95% CI: 0.53 to 1.46, p < 0.001); there were no between-group differences on forced vital capacity (SMD: 0.44, 95% CI: -0.01 to 0.88, p = 0.06), forced expiratory volume (SMD: 0.33, 95% CI: -0.12 to 0.77, p = 0.15), balance (SMD: 0.36, 95% CI: -0.04 to 0.77, p = 0.08), gait speed (SMD: 0.48, 95% CI: -0.44 to 1.40, p = 0.31), and trunk function (SMD: 0.79, 95% CI: -0.17 to 1.75, p = 0.11). Cervical mobilization significantly improved forward head posture; however, no significant differences were found in other outcomes. Clinicians may consider spinal mobilization as an adjunctive intervention in stroke rehabilitation to address posture-related impairments to expand treatment strategy and optimize quality of care.

Neutrophil and NETosis Modulation in Traumatic Heterotopic Ossification.

OBJECTIVE: To characterize the role of neutrophil extracellular traps (NETs) in heterotopic ossification (HO) formation and progression and to use mechanical and pharmacological methods to decrease NETosis and mitigate HO formation. BACKGROUND: Traumatic HO is the aberrant osteochondral differentiation of mesenchymal progenitor cells after traumatic injury, burns, or surgery. While the innate immune response has been shown to be necessary for HO formation, the specific immune cell phenotype and function remain unknown. Neutrophils, one of the earliest immune cells to respond after HO-inducing injuries, can extrude DNA, forming highly inflammatory NETs. We hypothesized that neutrophils and NETs would be diagnostic biomarkers and therapeutic targets for the detection and mitigation of HO. METHODS: C57BL6J mice underwent burn/tenotomy (a well-established mouse model of HO) or a non-HO-forming sham injury. These mice were either (1) ambulated ad libitum, (2) ambulated ad libitum with daily intraperitoneal hydroxychloroquine, ODN-2088 (both known to affect NETosis pathways), or control injections, or (3) had the injured hind limb immobilized. Single-cell analysis was performed to analyze neutrophils, NETosis, and downstream signaling after the HO-forming injury. Immunofluorescence microscopy was used to visualize NETosis at the HO site and neutrophils were identified using flow cytometry. Serum and cell lysates from HO sites were analyzed using enzyme-linked immunosorbent assay for myeloperoxidase-DNA and ELA2-DNA complexes to identify NETosis. Micro-computerized tomography was performed on all groups to analyze the HO volume. RESULTS: Molecular and transcriptional analyses revealed the presence of NETs within the HO injury site, which peaked in the early phases after injury. These NETs were highly restricted to the HO site, with gene signatures derived from both in vitro NET induction and clinical neutrophil characterizations showing a high degree of NET "priming" at the site of injury, but not in neutrophils in the blood or bone marrow. Cell-cell communication analyses revealed that this localized NET formation coincided with high levels of toll-like receptor signaling specific to neutrophils at the injury site. Reducing the overall neutrophil abundance within the injury site, either pharmacologically through treatment with hydroxychloroquine, the toll-like receptor 9 inhibitor OPN-2088, or mechanical treatment with limb offloading, results in the mitigation of HO formation. CONCLUSIONS: These data provide a further understanding of the ability of neutrophils to form NETs at the injury site, clarify the role of neutrophils in HO, and identify potential diagnostic and therapeutic targets for HO mitigation.

Outcome of Impella 2.5 use in patients undergoing Percutaneous Coronary Intervention in Henan, China: a case series.

BACKGROUND: Acute myocardial infarction (AMI) complicated by cardiogenic shock (AMI-CS) or heart failure is associated with an unacceptably high in-hospital mortality of 33%-55% and a lost chance to accept PCI (Percutaneous Coronary Intervention). AIM: The aim of the study was to find out whether percutaneous hemodynamic support device Impella 2.5 improves prognosis of high-risk PCI patients or not. METHODS: This study was a case series involving six patients who underwent a Left Ventricular Assist Device (LVAD, Impella 2.5, Abiomed, Danvers, MA) implantation after suffering from AMI with a very low ejection fraction and acute heart failure. The clinical experience and outcomes of the patients are hereby discussed. RESULTS: All PCI procedures were safely completed under LVAD support. The hemodynamic parameters of all patients improved clinically over the next 30 days and following 12 months after Impella insertion except in two patients, of which one patient (Case number 6) died 4 days post-Impella protected PCI procedure due to acute left ventricle heart failure with cardiogenic shock and pulmonary oedema; and another one died at 12 months after Impella protected PCI procedure (Case number 4) due to decompensated heart failure and infected pneumonia. CONCLUSION: Percutaneous hemodynamic support is favorable and feasible during high risk Percutaneous Coronary Intervention (PCI). A bigger study is needed to substantiate the claims of the current study.

GAS5/METTL14/ESR1 genetic variants are related to the susceptibility of coronary heart disease.

The prevention and treatment of coronary heart disease (CHD) is a difficult problem to be solved urgently. Genetic factors play a crucial role in CHD development. This study aimed to investigate the association of GAS5/METTL14/ESR1 polymorphisms with CHD susceptibility. We carried out a case-control study that included 506 patients and 506 healthy subjects to detect the correlation between GAS5/METTL14/ESR1 polymorphisms and CHD risk in a Chinese population. Odds ratios (OR) and 95% confidence intervals (CI) were computed to assess the associations. Our study showed that GAS5 rs17359906 (OR 2.32, p = 0.020) and rs75315904 (OR 0.41, p = 0.039) were related to the risk of CHD in females. ESR1 rs6927072 (OR 1.76, p = 0.007) and rs4870061 (OR 0.74, p = 0.036) correlated with CHD risk in age ≤ 60 years. GAS5 rs17359906 (OR 0.10, p = 0.032) and ESR1 rs3020308 (OR 2.73, p = 0.041) were associated with an increased susceptibility to CHD in smokers. We also found that METTL14 rs4834698 (OR 1.57, p = 0.044) and ESR1 rs4870061 (OR 0.62, p = 0.040) were associated with CHD susceptibility in non-drinkers. Besides, METTL14 rs17050450 (OR 0.48, p = 0.029) and ESR1 rs3853248 (OR 1.61, p = 0.018) had the susceptibility of CHD patients with diabetes. Our study indicated that GAS5/METTL14/ESR1 polymorphisms were associated with CHD risk, which might provide a new understanding of CHD in a Chinese population.

Preliminary Study of Genome-Wide Association Identified Novel Susceptibility Genes for Hemorheological Indexes in a Chinese Population.

Background: Genome-wide association studies for various hemorheological characteristics have not been reported. We aimed to identify genetic loci associated with hemorheological indexes in a cohort of healthy Chinese Han individuals. Methods: Genotyping was performed using Applied Biosystems Axiom™ Precision Medicine Diversity Array in 838 individuals, and 6,423,076 single nucleotide polymorphisms were available for genotyping. The relations were examined in an additive genetic model using mixed linear regression and combined with identical by descent matrix. Results: We identified 38 genetic loci (p < 5 × 10-6) related to hemorheological traits. In which, LOC102724502-OLIG2 rs28371438 was related to the levels of nd30 (p = 8.58 × 10-07), nd300 (p = 1.89 × 10-06), erythrocyte rigidity (p = 1.29 × 10-06), assigned viscosity (p = 6.20 × 10-08) and whole blood high cut relative (p = 7.30 × 10-08). The association of STK32B rs4689231 for nd30 (p = 3.85 × 10-06) and nd300 (p = 2.94 × 10-06) and GTSCR1-LINC01541 rs11661911 for erythrocyte rigidity (p = 9.93 × 10-09) and whole blood high cut relative (p = 2.09 × 10-07) was found. USP25-MIR99AHG rs1297329 was associated with erythrocyte rigidity (p = 1.81 × 10-06) and erythrocyte deformation (p = 1.14 × 10-06). Moreover, the association of TMEM232-SLC25A46 rs3985087 and LINC00470-METTL4 rs9966987 for fibrinogen (p = 1.31 × 10-06 and p = 4.29 × 10-07) and plasma viscosity (p = 1.01 × 10-06 and p = 4.59 × 10-07) was found. Conclusion: These findings may represent biological candidates for hemorheological indexes and contribute to hemorheological study.

Cooperative physical separation of oil and suspended solids from methanol-to-olefin wastewater: A pilot study.

Methanol-to-olefin (MTO) is an important non-petroleum chemical process for the preparation of light olefins. However, the MTO process consumes copious amounts of water and produces large amounts of untreated effluent. Therefore, the realization of efficient wastewater treatment and recycling is key to the green low-carbon development of MTO. Here, a cooperative process combining swirl regenerating micro-channel separation (SRMS) and combined fibrous coalescence (CFC) technologies was proposed to separate high contents of oil and suspended matter in MTO wastewater. Using a pilot device with a treatment capacity of 1 m3/h, the average oil content in MTO wastewater decreased from 750 mg/L to <30 mg/L, while the average content of suspended matter decreased from 108 mg/L to <15 mg/L. Compared with a commercial MTO wastewater treatment process (olefin production capacity of 0.6 million tons per annum), the proposed method could reduce wastewater discharges and costs by 57% and US$ 0.23 million per annum respectively. Equipment costs and operational energy consumption were also reduced by 30% and >95% respectively. The combined process may provide the basis for the green and sustainable treatment of MTO wastewater and its recycling.

Beclin-1-Dependent Autophagy Protects the Heart During Sepsis.

BACKGROUND: Cardiac dysfunction is a major component of sepsis-induced multiorgan failure in critical care units. Changes in cardiac autophagy and its role during sepsis pathogenesis have not been clearly defined. Targeted autophagy-based therapeutic approaches for sepsis are not yet developed. METHODS: Beclin-1-dependent autophagy in the heart during sepsis and the potential therapeutic benefit of targeting this pathway were investigated in a mouse model of lipopolysaccharide (LPS)-induced sepsis. RESULTS: LPS induced a dose-dependent increase in autophagy at low doses, followed by a decline that was in conjunction with mammalian target of rapamycin activation at high doses. Cardiac-specific overexpression of Beclin-1 promoted autophagy, suppressed mammalian target of rapamycin signaling, improved cardiac function, and alleviated inflammation and fibrosis after LPS challenge. Haplosufficiency for beclin 1 resulted in opposite effects. Beclin-1 also protected mitochondria, reduced the release of mitochondrial danger-associated molecular patterns, and promoted mitophagy via PTEN-induced putative kinase 1-Parkin but not adaptor proteins in response to LPS. Injection of a cell-permeable Tat-Beclin-1 peptide to activate autophagy improved cardiac function, attenuated inflammation, and rescued the phenotypes caused by beclin 1 deficiency in LPS-challenged mice. CONCLUSIONS: These results suggest that Beclin-1 protects the heart during sepsis and that the targeted induction of Beclin-1 signaling may have important therapeutic potential.

Integrated Analysis of the Altered lncRNAs and mRNAs Expression in 293T Cells after Ionizing Radiation Exposure.

Tissue and cell damage caused by ionizing radiation is often highly genotoxic. The swift repair of DNA damage is crucial for the maintenance of genomic stability and normal cell fitness. Long noncoding RNAs (lncRNAs) have been reported to play an important role in many physiological and pathological processes in cells. However, the exact function of lncRNAs in radiation-induced DNA damage has yet to be elucidated. Therefore, this study aimed to analyze the potential role of lncRNAs in radiation-induced DNA damage. We examined the expression profiles of lncRNAs and mRNAs in 293T cells with or without 8 Gy irradiation using high-throughput RNA sequencing. We then performed comprehensive transcriptomic and bioinformatic analyses of these sequencing results. A total of 18,990 lncRNAs and 16,080 mRNAs were detected in all samples. At 24 h post irradiation, 49 lncRNAs and 323 mRNAs were differentially expressed between the irradiation group and the control group. qRT-PCR was used to verify the altered expression of six lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the predicted genes were mainly involved in the histone mRNA metabolic process and Wnt signaling pathways. This study may provide novel insights for the study of lncRNAs in radiation-induced DNA damage.

Personalized objects can optimize the diagnosis of EMCS in the assessment of functional object use in the CRS-R: a double blind, randomized clinical trial.

BACKGROUND: Behavioral assessment has been acted as the gold standard for the diagnosis of disorders of consciousness (DOC) patients. The item "Functional Object Use" in the motor function sub-scale in the Coma Recovery Scale-Revised (CRS-R) is a key item in differentiating between minimally conscious state (MCS) and emergence from MCS (EMCS). However, previous studies suggested that certain specific stimuli, especially something self-relevant can affect DOC patients' scores of behavioral assessment scale. So, we attempted to find out if personalized objects can improve the diagnosis of EMCS in the assessment of Functional Object Use by comparing the use of patients' favorite objects and other common objects in MCS patients. METHODS: Twenty-one post-comatose patients diagnosed as MCS were prospectively included. The item "Functional Object Use" was assessed by using personalized objects (e.g., cigarette, paper) and non-personalized objects, which were presented in a random order. The rest assessments were performed following the standard protocol of the CRS-R. The differences between functional uses of the two types of objects were analyzed by the McNemar test. RESULTS: The incidence of Functional Object Use was significantly higher using personalized objects than non-personalized objects in the CRS-R. Five out of the 21 MCS studied patients, who were assessed with non-personalized objects, were re-diagnosed as EMCS with personalized objects (χ2 = 5, df = 1, p < 0.05). CONCLUSIONS: Personalized objects employed here seem to be more effective to elicit patients' responses as compared to non-personalized objects during the assessment of Functional Object Use in DOC patients. TRIAL REGISTRATION: Clinical Trials.gov: NCT02988206 ; Date of registration: 2016/12/12.

Autoimmune diseases and COPD risk: A Mendelian randomization study.

BACKGROUND: Studies in epidemiology have indicated a link between chronic obstructive pulmonary disease (COPD) and various autoimmune conditions.This study aimed to investigate the potential causal link between nine autoimmune diseases with a genetic basis and COPD using a two-sample Mendelian randomization (MR) analysis. METHOD: To test the impact of susceptibility to immune-related outcomes on genetic prediction of COPD risk, we used pooled statistics from the largest genome-wide association study (GWAS) in Europe in a two-sample MR setting.Genetic data for type 1 diabetes, hypothyroidism, systemic lupus erythematosus, and primary biliary cirrhosis were obtained from the European Bioinformatics Institute (EBI), while data for multiple sclerosis and primary sclerosing cholangitis were extracted from the Integrative Epidemiology Unit (IEU) database. Additionally, genetic data for ulcerative colitis, rheumatoid arthritis, and celiac disease were also collected.These nine autoimmune diseases and the COPD cohort from the UK Biobank (1605 cases and 461,328 controls) were analyzed separately as exposure and outcome.Our primary method for the initial screening was inverse variance weighting (IVW).The MR-Egger regression test assessed multivariate validity, while the Cochran's Q test examined heterogeneity.To ensure the reliability of the findings, a leave-one-out analysis was conducted. RESULT: IVW discovered proof of type 1 diabetes (OR = 1.0003; 95 % CI = 1.0000-1.0005; P = 0.046), hypothyroidism (OR = 1.0004; 95 % CI = 1.0001-1.0008; P = 0.0263), celiac disease (OR = 1.0002; 95 % CI = 1.0000-1.0004; P = 0.0168) and systemic lupus erythematosus (OR = 1.0002; 95 % CI = 1.0000-1.0004; P = 0.049) were significantly linked to the heightened risk of COPD with no signs of variation or pleiotropy.Even after accounting for potential confounding factors like smoking, the correlation remained robust.Additionally, our research found that the IVW method did not indicate any causal link between COPD and multiple sclerosis, ulcerative colitis, rheumatoid arthritis, primary biliary cirrhosis, or primary sclerosing cholangitis (all P >0.05). CONCLUSION: This research discovered that individuals with type 1 diabetes, hypothyroidism, celiac disease, and systemic lupus erythematosus have a higher likelihood of developing COPD.Additionally, this research revealed no connection between COPD and multiple sclerosis, ulcerative colitis, rheumatoid arthritis, primary biliary cirrhosis, or primary sclerosing cholangitis.

Efficacy and safety of tirzepatide versus placebo in overweight or obese adults without diabetes: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Tirzepatide was approved to treat type 2 diabetes and obesity, but its efficacy and safety in patients without diabetes has not been investigated. AIM: This meta-analysis aimed to evaluate the efficacy and safety of tirzepatide compared to placebo in overweight or obese patients without diabetes. METHOD: PubMed, Embase and Cochrane were searched on January 18, 2024. Randomized controlled trials (RCTs) that used tirzepatide in overweight or obese adults without diabetes were included. Efficacy outcomes included the proportion of participants achieving weight loss targets, changes in body weight (%), body mass index (BMI), waist circumference (WC), and blood pressure (BP). Safety outcomes were commonly reported adverse events. Standardized mean differences (SMD) or odds ratios (OR) with 95% confidence intervals (CIs) were used for continuous and dichotomous outcomes, respectively. RESULTS: Three RCTs with 3901 participants were included. Tirzepatide was associated with increased proportion of participants achieving weight loss targets, reduced body weight (SMD - 1.61, 95% CI - 2.20 to - 1.02), BMI (SMD - 2.13, 95% CI - 3.08 to - 1.18), WC (SMD - 0.91, 95% CI - 1.14 to - 0.69), and BP versus placebo. However, the risk of adverse events such as nausea (OR 4.26, 95% CI 2.60 to 3.81), vomiting (OR 8.35, 95% CI 5.19 to 13.45), and diarrhea (OR 3.57, 95% CI 2.80 to 4.57) was significantly higher for tirzepatide versus placebo. CONCLUSION: Tirzepatide significantly reduced weight and improved metabolic markers among overweight or obese without diabetes. However, increased adverse events highlights the need for benefits versus risks assessment before initiation and continuous monitoring.

Meta-analysis of the therapeutic effect of electrical stimulation combined with pelvic floor muscle exercise on female pelvic floor dysfunction.

OBJECTIVES: To systematically evaluate the therapeutic effect of electrical stimulation combined with pelvic floor muscle exercise on female pelvic floor dysfunction (PFD). METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was applied. A computer-based retrieval was performed in the databases of PubMed, Web of Science, Embase, and Cochrane Library from database establishment to September 15, 2023, to identify randomized controlled trials on electrical stimulation combined with pelvic floor muscle function exercise on female PFD. Literature screening, data extraction, and quality evaluation were performed independently by two researchers, and meta-analysis was performed using the statistical software Stata15.0. RESULTS: 1. In total, 12 randomized controlled trials were included, involving 721 female patients. The overall quality of methodologies employed in the included studies was relatively high. 2. Meta-analysis results showed that electrical stimulation combined with pelvic floor muscle exercise could effectively mitigate the severity of female PFD (SMD = -1.01, 95% CI - 1.78, - 0.25, P < 0.05). 3. This combination treatment demonstrated a significant positive effect on the improvement of pelvic floor muscle strength in female patients (P < 0.05); however, it had no significant effect on the improvement in quality of life (P > 0.05). CONCLUSIONS: Compared with pelvic floor muscle exercise alone, electrical stimulation combined with pelvic floor muscle exercise could effectively mitigate the severity of female PFD. It had a notable positive impact on enhancing pelvic floor muscle strength in female patients, although it did not significantly improve quality of life. Future high-quality studies are warranted.

Causal Relationships Between Emotional Instability and Respiratory Diseases: A Mendelian Randomization Analysis.

Background: In the past few years, there has been a growing fascination with the connection between mental well-being and respiratory conditions. However, the causal relationship between personality traits and respiratory diseases remains largely unknown. This study aimed to investigate the link between genetically predicted emotional instability and eight respiratory conditions using a two-sample Mendelian randomization (MR) analysis. Methods: In a GWAS dataset from the UK Biobank, SNPs linked to emotional instability were discovered among 204,412 participants of European descent. Genetic information for lung cancer, pulmonary fibrosis, pneumonia, and bronchiectasis was obtained from the European Bioinformatics Institute (EBI). While data for chronic obstructive pulmonary disease (COPD), pulmonary embolism, chronic cough, and asthma was collected from the UK BioBank. An MR study was carried out to investigate how specific single nucleotide polymorphisms (SNPs) impact the likelihood of developing the eight respiratory conditions listed. Our main approach for the initial screening was the utilization of inverse variance weighting (IVW). Multiplicity was assessed using the MR-Egger regression test, while heterogeneity was evaluated with Cochran's Q test. To ensure the reliability of the findings, a leave-one-out analysis was conducted. Results: IVW found evidence that emotional instability had a significant causal effect on the increased risk of COPD (OR = 1.009; 95% CI = 1.001-1.017; P = 0.022), pneumonia (OR = 1.648; 95% CI = 1.036-2.622; P = 0.035), chronic cough (OR = 1.077; 95% CI = 1.013-1.145; P = 0.017) and increased risk of asthma (OR = 1.073; 95% CI = 1.026-1.123; P = 0.002) had a significant causal relationship. This association remained strong in the case of potential confounders, including smoking. Additionally, the instrumental variable weighted method in this study did not find any indication of a causal link between emotional instability and lung cancer, pulmonary embolism, pulmonary fibrosis, and bronchiectasis (all P > 0.05). Conclusion: The research discovered a link between emotional instability and a higher likelihood of developing COPD, pneumonia, chronic cough, and asthma. This study also found that emotional instability was not causally associated with lung cancer, pulmonary embolism, pulmonary fibrosis, and bronchiectasis.

Direct and Indirect Costs of Breast Cancer and Associated Implications: A Systematic Review.

INTRODUCTION: Breast cancer is currently the leading cause of global cancer incidence. Breast cancer has negative consequences for society and economies internationally due to the high burden of disease which includes adverse epidemiological and economic implications. Our aim is to systematically review the estimated economic burden of breast cancer in the United States (US), Canada, Australia, and Western Europe (United Kingdom, France, Germany, Spain, Italy, Norway, Sweden, Denmark, Netherlands, and Switzerland), with an objective of discussing the policy and practice implications of our results. METHODS: We included English-language published studies with cost as a focal point using a primary data source to inform resource usage of women with breast cancer. We focussed on studies published since 2017, but with reported costs since 2012. A systematic search conducted on 25 January 2023 identified studies relating to the economic burden of breast cancer in the countries of interest. MEDLINE, Embase, and EconLit databases were searched via Ovid. Study quality was assessed based on three aspects: (1) validity of cost findings; (2) completeness of direct cost findings; and (3) completeness of indirect cost findings. We grouped costs based on country, cancer stage (early compared to metastatic), and four resource categories: healthcare/medical, pharmaceutical drugs, diagnosis, and indirect costs. Costs were standardized to the year 2022 in US (US$2022) and International (Int$2022) dollars. RESULTS: Fifty-three studies were included. Studies in the US (n = 19) and Canada (n = 9) were the majority (53%), followed by Western European countries (42%). Healthcare/medical costs were the focus for the majority (89%), followed by pharmaceutical drugs (25%), then diagnosis (17%) and indirect (17%) costs. Thirty-six (68%) included early-stage cancer costs, 17 (32%) included metastatic cancer costs, with 23% reporting costs across these cancer stages. No identified study explicitly compared costs across countries. Across cost categories, cost ranges tended to be higher in the US than any other country. Metastatic breast cancer was associated with higher costs than earlier-stage cancer. When indirect costs were accounted for, particularly in terms of productivity loss, they tended to be higher than any other estimated direct cost (e.g., diagnosis, drug, and other medical costs). CONCLUSION: There was substantial heterogeneity both within and across countries for the identified studies' designs and estimated costs. Despite this, current empirical literature suggests that costs associated with early initiation of treatment could be offset against potentially avoiding or reducing the overall economic burden of later-stage and more severe breast cancer. Larger scale, national, economic burden studies are needed, to be updated regularly to ensure there is an ongoing and evolving perspective of the economic burden of conditions such as breast cancer to inform policy and practice.

Vegfc-expressing cells form heterotopic bone after musculoskeletal injury.

Heterotopic ossification (HO) is a challenging condition that occurs after musculoskeletal injury and is characterized by the formation of bone in non-skeletal tissues. While the effect of HO on blood vessels is well established, little is known about its impact on lymphatic vessels. Here, we use a mouse model of traumatic HO to investigate the relationship between HO and lymphatic vessels. We show that injury triggers lymphangiogenesis at the injury site, which is associated with elevated vascular endothelial growth factor C (VEGF-C) levels. Through single-cell transcriptomic analyses, we identify mesenchymal progenitor cells and tenocytes as sources of Vegfc. We demonstrate by lineage tracing that Vegfc-expressing cells undergo osteochondral differentiation and contribute to the formation of HO. Last, we show that Vegfc haploinsufficiency results in a nearly 50% reduction in lymphangiogenesis and HO formation. These findings shed light on the complex mechanisms underlying HO formation and its impact on lymphatic vessels.

Mesenchymal stem cell-derived extracellular vesicles targeting irradiated intestine exert therapeutic effects.

Background: Radiation-induced intestinal injuries are common in patients with pelvic or abdominal cancer. However, these injuries are currently not managed effectively. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been extensively used in regenerative medicine. However, the results of MSC-EVs in the repair of radiation-induced intestinal damage have been unsatisfactory. We here investigated the nanotherapeutic functions of MSC-EVs in radiation-induced intestinal injury. Methods: We visualized the biodistribution and trend of MSC-EVs through in vivo imaging. A radiation-induced intestinal injury model was constructed, and the therapeutic effect of MSC-EVs was explored through in vivo and in vitro experiments. Immunofluorescence and qRT-PCR assays were conducted to explore the underlying mechanisms. Results: MSC-EVs exhibited a dose-dependent tendency to target radiation-injured intestines while providing spatiotemporal information for the early diagnosis of the injury by quantifying the amount of MSC-EVs in the injured intestines through molecular imaging. Meanwhile, MSC-EVs displayed superior nanotherapeutic functions by alleviating apoptosis, improving angiogenesis, and ameliorating the intestinal inflammatory environment. Moreover, MSC-EVs-derived miRNA-455-5p negatively regulated SOCS3 expression, and the activated downstream Stat3 signaling pathway was involved in the therapeutic efficacy of MSC-EVs in radiation-induced intestinal injuries. Conclusion: MSC-EVs can dose-dependently target radiation-injured intestinal tissues, allow a spatiotemporal diagnosis in different degrees of damage to help guide personalized therapy, offer data for designing EV-based theranostic strategies for promoting recovery from radiation-induced intestinal injury, and provide cell-free treatment for radiation therapy.